BIBF 1120 for Recurrent High-Grade Gliomas

NCT01380782 | Completed Phase 2 Results DMC

• 2 other identifiers: 11-055BIBF 1199.94
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 4

Brief Summary

BIBF 1120 is a newly discovered compound that may stop cancer cells from growing abnormally. This drug is currently being used in treatment for other cancers in research studies and information from those other research studies suggests that this agent, BIBF 1120, may help to stop recurrent malignant glioma cells from multiplying and it may also prevent the growth of new blood vessels at the site of the tumor. In this research study, the investigators are looking to see how well BIBF 1120 works in patients with recurrent malignant gliomas.

Conditions

Glioblastoma; Gliosarcoma; Anaplastic Astrocytoma; Anaplastic Oligodendroglioma; Anaplastic Oligoastrocytoma

Keywords

brain tumor; recurrent disease

Outcome Measures

Primary Outcomes (2)

• 6-Month Progression Free Survival

  To determine the efficacy of BIBF 1120 in bevacizumab-naive participants with recurrent glioblastoma (GBM) as measured by 6-month progression-free survival (PFS6).

  Six months

• 3-Month Progression Free Survival

  To determine the efficacy of BIBF 1120 in bevacizumab-treated participants with recurrent GBM as measured by 3-month progression free survival (PFS3).

  3 months

Secondary Outcomes (4)

• Proportion of Participants Experiencing Stable Disease (SD) as Their Best Radiographic Response

  2 years

• Overall Survival

  2 years

• Time-to-tumor Progression

  2 years

• Safety Profile as Summarized With Descriptive Statistics (Using Toxicity Data Gathered on Trial)

  2 years

Other Outcomes (4)

• Exploratory Objective #1: Progression-free Survival at 3- and 6-months for Participants With Recurrent Anaplastic Gliomas (AG)

  Arm A - 6 months; Arm B - 3 months

• Exploratory Objective #2: Determination if Any Correlation Exists Between Patient Outcomes (Survival, PFS3, PFS6) and Tumor Genotype and/or Expression Profile

  2 years

• Exploratory Objective #3: Determination if Any Correlation Exists Between Patient Outcomes (Survival, PFS3, PFS6) and Serum Angiogenic Peptides, Circulating Endothelial Cells, and/or Circulating Progenitor Cells

  2 years

Study Arms (2)

Bevacizumab Naive

EXPERIMENTAL

Bevacizumab naive subjects

Drug: BIBF 1120

Prior Bevacizumab

EXPERIMENTAL

Patients previously treated with bevacizumab

Drug: BIBF 1120

Interventions

BIBF 1120 DRUG

200 mg BID oral for 28 day cycle

Bevacizumab Naive; Prior Bevacizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histopathologically-confirmed, supratentorial, recurrent glioblastoma; subjects with an initial diagnosis of a lower grade glioma are eligible if a subsequent biopsy is determined to be glioblastoma
• Demonstration of recurrent disease on MRI following prior therapy
• Development of progressive disease after having received prior RT, and must have an interval of at least 12 weeks from the completion of any radiation therapy to study entry (unless progressive tumor growth is outside the radiation field or there is histopathological confirmation of recurrent tumor).
• Bi-dimensionally measurable disease (minimum measurement of 1 cm in one dimension) on MRI performed within 14 days prior to first treatment. (If receiving corticosteroids, participants must be on a stable or decreasing dose of corticosteroids for at least 5 days prior to baseline MRI.)
• Life expectancy of at least 12 weeks
• KPS \>/= 60
• Normal organ and marrow function as defined by protocol
• Recovered from toxic effects of prior therapy
• Sufficient tumor availability (at least 15-20 unstained paraffin slides from any prior surgery)

You may not qualify if:

• Receiving other investigational agent
• More than 2 prior relapses
• Prior therapy with inhibitor of VEGF, VEGFR, PDGFR, or FGFR (including bevacizumab)
• Pregnant or breast-feeding
• Unwilling to agree to adequate contraception, if subject is of child-bearing potential
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to BIBF 1120
• Use of EIAEDs within 14 days of registration
• Evidence of recent hemorrhage on baseline MRI of the brain
• Uncontrolled intercurrent illness
• Uncontrolled hypertension
• History of hypertensive encephalopathy
• History of any of the following within 6 months prior to enrollment: myocardial infarction or unstable angina, stroke or transient ischemic attack, significant vascular disease or peripheral arterial thrombosis, abdominal fistula, gastrointestinal perforation, or intra-abdominal abcess, intracerebral abscess
• Evidence of bleeding diathesis or coagulopathy
• Major surgical procedure, open biopsy, or significant traumatic injury within 4 weeks prior to the first treatment day, or anticipation of need for major surgical procedure during the course of the study
• Minor surgical procedures, stereotactic biopsy, fine needle aspiration, or core biopsy within 7 days prior to the first treatment day

Sponsors & Collaborators

• Patrick Y. Wen, MD: lead
• Boehringer Ingelheim: collaborator
• Wake Forest University Health Sciences: collaborator
• University of Virginia: collaborator
• Massachusetts General Hospital: collaborator
• The Cleveland Clinic: collaborator

Study Sites (4)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

University of Virginia

Charlottesville, Virginia, 22908-4324, United States

Location

Related Publications (1)

• Norden AD, Schiff D, Ahluwalia MS, Lesser GJ, Nayak L, Lee EQ, Rinne ML, Muzikansky A, Dietrich J, Purow B, Doherty LM, LaFrankie DC, Pulverenti JR, Rifenburg JA, Ruland SF, Smith KH, Gaffey SC, McCluskey C, Ligon KL, Reardon DA, Wen PY. Phase II trial of triple tyrosine kinase receptor inhibitor nintedanib in recurrent high-grade gliomas. J Neurooncol. 2015 Jan;121(2):297-302. doi: 10.1007/s11060-014-1631-y. Epub 2014 Oct 22.

  PMID: 25338318 DERIVED

MeSH Terms

Conditions

Glioblastoma; Gliosarcoma; Astrocytoma; Oligodendroglioma; Brain Neoplasms; Recurrence

Interventions

nintedanib

Condition Hierarchy (Ancestors)

Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Limitations and Caveats

The trial intended to enroll 14 participants onto Arm A GBM, but only 10 enrolled due to futility. In addition, 10 AG participants were to be enrolled onto each Arm as exploratory cohorts, but again due to futility only 4 enrolled onto Arm B.

Results Point of Contact

• Title: Patrick Y. Wen, MD
• Organization: Dana-Farber Cancer Institute

pwen@partners.org

6176322166

Study Officials

• Patrick Y Wen, M.D.

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Director, Center for Neuro-Oncology

Study Record Dates

• First Submitted: June 21, 2011
• First Posted: June 27, 2011
• Study Start: May 1, 2012
• Primary Completion: July 1, 2013
• Study Completion: July 1, 2014
• Last Updated: August 18, 2014
• Results First Posted: August 18, 2014

Record last verified: 2014-08

Locations

US (4)